In the field of cancer therapy, targeting therapy against a specific type of cancer cell has been studied so far for the treatment of solid cancer on which no therapeutic agent shows sufficient effect. In such targeting therapy, a monoclonal antibody that specifically recognizes cancer cells is effective. However, the use of a mouse monoclonal antibody has some problems such as difficulty of repetitive administration because of side effects such as anaphylaxis caused by an immune response (Proc. Natl. Acad. Sci. U.S.A. vol.86, p 4220, 1989).
For solving such problems, attempts have been conducted to obtain monoclonal antibodies with reduced side effects. A technology for producing a chimeric antibody in which constant region is replaced with that of human antibody by genetic engineering, a technology for producing a humanized antibody in which all regions except for hypervariable regions are replaced with those of human antibody, etc. are known. However, a complete human monoclonal antibody has been desired from the viewpoint of reducing side effects. As a method of obtaining a complete human monoclonal antibody, there is a hybridoma method using a lymphocyte derived from human (Cancer Res. vol.45, p 263, 1985). Although there is a few report about a human monoclonal antibody that reacts cancer cells (JP3236667 etc.), preparation of human monoclonal antibodies which adequately react with cancer cells has been still very difficult because of the reasons that it is very difficult to conduct passive immunity for the purpose of obtaining human B cells which produce a desired antibody, and that any efficient methodology which allows infinite reproduction of antibody-producing cells has not been established yet.
Even under such circumstances, some monoclonal antibodies which exhibit a killing-effect or anti-proliferative effect on specific cancer cells by itself or in combination with anti-cancer drugs have been developed using a humanized antibody technology or the like. In recent years, application of an anti-Her2-humanized antibody HERCEPTIN™) to breast cancer (Oncology vol. 63 Suppl 1, pp 25-32, 2002), clinical trials using an anti-EGF receptor antibody (Semin Oncol. vol. 29, No. 5 Suppl 14, pp 18-30, 2002), or an anti-VEGF (vascular endothelial growth factor) antibody (Semin Oncol. vol. 29, No. 6 Suppl 16, pp 10-14, 2002), and the like have been reported. However, any antibody, which can be used for targeting therapy for cancers including a non-small cell lung cancer from which many patients are suffering or refractory cancers such as pancreatic cancer, has not yet been developed. For treating such types of cancer, the acquisition of a monoclonal antibody having high specificity to cancer tissue with reduced side effects has been desired.
Vimentin is a cytoskeletal filament protein of a mesenchymal or nonepithelial cell, and it is known that its gene expression increases upon cell stimulation (Mol Cell Biol. 1987, vol. 7, No. 11, p3908-15). In addition, it is known that the expression of vimentin is not found in normal epithelial cells, whereas high expression of vimentin is found in cytoplasm of some poorly-differentiated tumor cells such as those of pulmonary adenocarcinoma, gastric cancer, endometrial carcinoma, or embryonal cell carcinoma (Mol Cell Biol. 1987, vol. 7, No. 11, p 3908-15). However, a phenomenon that vimentin functions as an antigenic protein has not been known.